BACKGROUND

The bullous variant of Darier’s disease (DD) is a rare type with clinical and histological features suggestive of Hailey-Hailey disease (HHD).1 It is a rare form, initially described by Pels and Goodman in 1939.2 There were only few similar reported cases.1–6 The following case report describes two cases of DD characterized by predominant flexural distribution and a bullous form, in one case, clinically and histologically mimicking HHD.

CASE REPORT 1

A 51-year-old woman with no past medical history presented with pruritic lesions involving the flexural areas. Informed consent was obtained from the patient. She reported that her father and her daughter had similar skin lesions on skin folds. Her three other children were healthy. Cutaneous examination revealed erythematous plaques, with macerated and eroded surface, partially covered by small blisters in axillary and inguinal areas, with parallel rhagades on the groins and the internal aspects of the thighs (Figure 1). Palms, soles, oral and genital mucosa, and nails were normal. Histopathological examination of a biopsy specimen revealed suprabasal clefting with acantholysis, and a few foci resembling a ǃ·dilapidated brick wall.ǃ? Rare dyskeratotic cells were also observed with ǃ·corps rondsǃ? in the stratum spinosum (Figure 2). Direct immunofluorescence on cutaneous biopsy was negative. The diagnosis of HHD was proposed. The patient was treated with topical antimicrobials, which lead to complete healing of the erosions, leaving no macroscopic changes, other than a temporary pigmentation. A relapse occurred one year later with a rapid improvement under topical antimicrobials.

Figure 1.
figure 1

Erythematous plaques, with parallel rhagades on the groins and the internal aspects of the thighs.

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Figure 2
figure 2

Suprabasal clefting with acantholysis, and few foci resembling to a ǃ·dilapidated brick wall.ǃ?

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CASE REPORT 2

The second report concerned the first patient’s daughter, a 25-year-old with no past medical history, who presented with itching papules of skin folds. Informed consent was obtained from her. Cutaneous examination revealed greasy brown-colored and keratotic papules of 1ǃÏ3 mm in diameter, occupying the axillary and infra-mammary folds (Figure 3). These lesions had begun 5 years ago and remained unchanged since that time, except for a slight exacerbation by heat, sweating, or friction. Cutaneous examination was otherwise normal; with no mucosal or nail abnormalities. The histopathological examination of a cutaneous biopsy of one of the keratotic lesions revealed suprabasal clefts of the epidermis with acantholysis. There were also hyperkeratosis and focal dyskeratosis (premature cornification with detached ǃÚcorps ronds’) (Figure 4A, Figure 4B). The patient was treated with topical retinoid, which led to a partial clearance.

Figure 3
figure 3

Keratotic brown-colored papules in the infra-mammary folds

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Figure 4
figure 4

Suprabasal clefts with acantholysis, hyperkeratosis and focal dyskeratosis.

A

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In view of the clinical and pathological findings in the mother and daughter, a diagnosis of DD was made in both patients. Bullous DD of the flexural areas was diagnosed in the mother.

DISCUSSION

In bullous DD the clinical and histopathological findings are often suggestive of HHD. DD and HHD are both autosomal dominant calcium adenosine triphosphate synthase (ATPase) disorders. Even though they share some clinical and histopathological features, they correspond to two genetically distinct entities, and the presence of the two disorders in the same family seems to be unlikely. The authors believe that the previous reports of patients described as having both DD and HHD were probably cases of DD with flexural involvement.7,8

DD often begins in childhood before the age of twenty, and lesions develop slowly and remain static with no permanent clearance.9 In HHD, lesions, however, develop rapidly and may disappear entirely, leaving no residual lesions, except for temporary pigmentation.10 Histologically, acantholytic suprabasal clefts can be seen in both disorders, but in HHD, acantholysis is usually incomplete, causing the well known ǃ·dilapidated brick wallǃ? appearance of the lower epidermis. Moreover, predominant dyskeratotic keratinocytes in DD can be a distinctive histological feature between these two genodermatoses.11 The bullous variant of DD is characterized by histological overlap with HHD, given the presence of extended acantholysis with foci of ǃ·dilapidated brick wallǃ? appearance and few dyskeratotic cells, as shown in our first presented patient, who also has a striking clinical resemblance with HHD. Our first patient had a late onset-flexural involvement with a relapsing course of the vesicles, leading to eroded surface, covered by parallel rhagades. All of these signs together with the presence of foci of ǃ·dilapidated brick wallǃ? and the lack of profound dyskeratosis were in favor of HHD. However, this diagnosis was corrected by examining the daughter who presented with typical clinical and histological features of DD. The correlation of clinical and histopathological features in the mother and the daughter led to the diagnosis of bullous DD in the mother.

The clinical and histopathological findings suggestive of HHD in cases of bullous DD have been previously reported.7,8 The current therapeutic alternatives for DD are based on keratolytic drugs, topical antimicrobials for infections, topical retinoids to reduce hyperkeratosis, and oral retinoids for severe cases, with variable clinical responses.12 In bullous DD, management should be different from that of the classic form and should take into account the risk of aggravation of macerated lesions by classic topical and systemic treatments. Our first patient with bullous DD demonstrated a complete clearance of erosions under topical antimicrobials. The second patient was treated with topical retinoid with only a partial improvement.

CONCLUSION

The diagnosis of vesiculo-bullous DD is difficult in view of the histological and clinical overlap with HHD. Subtle clinical and histological analysis may aid correct diagnosis and in doubt, molecular diagnosis is mandatory.